The Role of Calcium Dysregulation in Anesthetic-Mediated Neurotoxicity

Increasing evidence suggests that general anesthetics, either volatile or IV, can induce cell death by apoptosis in a concentration- and time-dependent manner in different types of cells, including neurons, in various animal models. Neurons in the developing brain are especially vulnerable to anesthetic-mediated neurodegeneration. For example, isoflurane, at clinically relevant concentrations, induces widespread neuronal apoptosis in the developing rat brain with subsequent learning deficits. This cognitive dysfunction after exposure to isoflurane has been shown to persist for several weeks in both adult and aged rats and mice. Frequently used IV anesthetics, such as ketamine and propofol, also induce cell death in cell culture and animal models, including primates. The mechanisms of anesthetic-mediated neuroapoptosis are still not clear. One emerging mechanism for anesthetic-mediated neurotoxicity, as illustrated by new work from Zhao et al. and Sinner et al. in this issue of the Journal, is disruption of the intracellular calcium homeostasis resulting in neuronal apoptosis.